We are continuing our studies on the interaction of bacteria and mammalian cells with particular emphasis on those factors which influence host cell resistance to infection both in vitro and in vivo. Although there is a correlation between the virulence of morphologic types 1 and 2 of N. gonorrhoeae and the presence of pili on their surface, the biochemical and genetic basis for this correlation is not understood. The non-infectious gonococcal strains types 3 and 4 are non-piliated. Under laboratory conditions, isolation of the gonococcus from infected patients rapidly changes from colonial morphologic types 1 and 2 to types 3 and 4. We plan to determine if the apparent loss of pili is related to other surface changes and other biochemical differences. The production of pili in other bacteria is known to be plasmid-DNA-directed. We are now comparing isolated plasmids from piliated and non-piliated gonococci. Further investigations are being carried out to define the specificity of the interaction between piliated gonococci and mammalian cells in relation to their ability for uptake and intracellular growth of the gonococcus.